Agent Orange as a risk factor for high‐grade prostate cancer

Abstract

PURPOSE Agent Orange exposure (AOe) is a potential risk factor for the development of prostate cancer (PCa). However, it is unknown whether AOe specifically increases the risk of lethal PCa. This study aimed to determine the association between AOe and the risk of detecting high-grade PCa (HGPCa, Gleason ≥ 7) on biopsy in a US Veteran cohort. METHODS Risk factors included clinico-demographic and laboratory data from veterans referred for an initial prostate biopsy. Outcomes were defined as the presence versus the absence of PCa, HGPCa, or low-grade PCa (LGPCa, Gleason ≤6) in biopsy specimens. Risk amongst AOe veterans relative to unexposed veterans was estimated with multivariate logistic regression. Separate models determined whether AOe was associated with an increased risk of PCa, HGPCa or LGPCa. RESULTS Of 2720 Veterans biopsied, PCa was diagnosed in 896 (32.9%); 459 (16.9%) had HGPCa. AOe was associated with a 52% increase in overall risk of PCa detection (aOR = 1.52, 95% CI: 1.07–2.13). AOe did not confer an increase in risk of LGPCa (aOR = 1.24, 95% CI: 0.81 to 1.91), although a 75% increase in risk of HGPCa (aOR = 1.75, 95% CI: 1.12 to 2.74) was observed. AOe was associated with a 2.1 fold increase (95% CI: 1.22 to 3.62, p<0.01) in Gleason 8 or higher PCa. CONCLUSION The increased risk of PCa associated with AOe is driven by an increased risk of HGPCa in men undergoing initial prostate biopsy. These findings could aid in improved PCa screening for Vietnam-era Veterans.

Dysbiosis signatures of the microbial profile in tissue from bladder cancer

“…Pesticides have been shown to lead to human cancer. For example, the pesticides that have alkyl ureas or amines are connected to brain tumors; dieldrin induces tumorigenesis of the lung, liver, lymphoid tissues, uterus, as well as thyroid; and the risk for prostate cancer is higher in patients exposed to Agent Orange . A prior investigation revealed that a trivalent pesticide‐related chemical can cause protein carbonylation and oxidative DNA damage in human urothelial cells, ultimately resulting in bladder cancer …”

A Review of Prostate Cancer Screening Guidelines for African American Veterans

“…Men exposed to Agent Orange were also diagnosed at a younger age compared to men who were not exposed to the carcinogen. In conclusion, exposure to Agent Orange appears to increase the detection of prostate cancer and incidence of high-grade prostate cancer; however, one must be cautious that these findings are not, at least partially, explained by selection bias [32].…”

“…During this period, the military used large amounts of a defoliant called Agent Orange to eliminate forest cover. In a study conducted at Portland Medical Center and Oregon Health Sciences University, it was found that veterans exposed to Agent Orange were not only more likely to develop prostate cancer, but also more likely to develop a more aggressive form of the disease [32]. Agent Orange exposure is associated with a 52% increase in the detection of prostate cancer and a 75% increased risk of high-grade prostate cancer [32].…”

Agent Orange and long-term outcomes after radical prostatectomy

“…Furthermore, the patients exposed to AO developed PC at a younger age and had more aggressive pathology when compared with their unexposed counterparts [9]. Similarly, Ansbaugh et al [10] demonstrated an increased risk of high-grade PC on biopsy and suggested that AO exposure could be used to intelligently screen patients for PC.…”